Tumor cells are capable of limiting antitumor CD8 + T cell responses through their cell surface expression of PD-L1. In addition to PD-1 expressed by CD8 + T cells, PD-L1 also binds to CD80 expressed by CD8 + T cells. The influence of the PD-L1/CD80 interaction on CD8 + T cell function has not been fully characterized, so we sought to investigate the impact of the PD-L1/CD80 interaction on PD-L1-induced apoptosis of activated CD8 + T cells. We found that CD8 + T cells that lacked CD80 expression got activated to the same extent as wild-type CD8 + T cells, but when cultured with anti-CD3 and PD-L1/Fc protein, activated CD8 + T cells that lacked CD80 expression survived better than activated wild-type CD8 + T cells. These findings indicate that PD-L1 induces apoptosis in activated CD8 + T cells in part by signaling through CD80. Thus, in the design and implementation of checkpoint blockade therapies that target PD-L1, it is essential that both binding partners for PD-L1, PD-1, and CD80 are considered.
Bibliographical noteFunding Information:
This work was supported by the Office of the Vice President for Research of the University of Minnesota (Grant-in-Aid of Research, Artistry, and Scholarship), by the University of Minnesota Undergraduate Research Opportunity Program, and by the Howard Hughes Medical Institute Precollege and Undergraduate Science Education Program. Special thanks are due to Brad Mondloch, Ellie Hofer, Matthew Molenaar, Tracie Weber, Alex Stangel, Charlie Peeters, Michael Maudal, Richard Bellefeuille, Tristane Paulson, Torri Jordan, Samuel Peters, Tarlynn Tone-Pah-Hote, Mariah Christopherson, Grace Pratt, McKenna Vininski, Mackenzie Schara, and Prince Nwaonicha for their contributions to this project.
© 2017 Meagan R. Rollins and Rachel M. Gibbons Johnson.